chr19-40458392-C-A

Variant names:

• chr19-40458392-C-A
• rs865805057
• NM_000713.3:c.233G>T

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_000713.3(BLVRB):​c.233G>T​(p.Arg78Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000697 in 1,434,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R78H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: BLVRB NM_000713.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.89
• Publications: 0 publications found

Genes affected

BLVRB (HGNC:1063): (biliverdin reductase B) Enables biliverdin reductase (NAD(P)+) activity and riboflavin reductase (NADPH) activity. Involved in heme catabolic process. Located in cytosol; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM1: In a mutagenesis_site Decreased affinity for coenzyme A. (size 0) in uniprot entity BLVRB_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.818

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000713.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLVRB	NM_000713.3	MANE Select	c.233G>T	p.Arg78Leu	missense	Exon 2 of 5	NP_000704.1	P30043

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLVRB	ENST00000263368.9	TSL:1 MANE Select	c.233G>T	p.Arg78Leu	missense	Exon 2 of 5	ENSP00000263368.3	P30043
	BLVRB	ENST00000643519.1		c.233G>T	p.Arg78Leu	missense	Exon 2 of 4	ENSP00000494515.1	A0A2R8YEP4
	BLVRB	ENST00000926837.1		c.233G>T	p.Arg78Leu	missense	Exon 2 of 5	ENSP00000596896.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434582 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 711172

African (AFR) AF: 0.00 AC: 0 AN: 32988

American (AMR) AF: 0.00 AC: 0 AN: 41030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25446

East Asian (EAS) AF: 0.00 AC: 0 AN: 38382

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 82244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099460

Other (OTH) AF: 0.00 AC: 0 AN: 59254

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		6.9
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.24
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.12	T
Polyphen		0.70	P
Vest4		0.38
MutPred		0.79		Loss of solvent accessibility (P = 0.0544)
MVP		0.50
MPC		0.28
ClinPred		0.98	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.76
gMVP		0.68
Mutation Taster		=36/64	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs865805057; hg19: chr19-40964299;